Hepatitis B Virus (HBV) is a non-cytopathic DNA virus that infects humans and may result in two clinical outcomes. In the majority of clinical infections in adults (90-95%), the virus is cleared after several weeks or months, and the patient develops a lifelong immunity against re-infection. In the remaining cases, however, the virus is not eliminated from the tissues, and the patient remains chronically infected. The sequence of chronic infection are serious: such individuals are highly likely to develop scarring of the liver tissue (cirrhosis) and may eventually develop hepatocellular carcinoma.
There is a prophylactic vaccine against HBV, and many developed countries have implemented childhood vaccination programs to reduce the overall risk of infection. Unfortunately, since the morbidity and mortality resulting from chronic HBV infection occurs over a period of decades, the impact of vaccination will not be realized until well into the future. Indeed, the annual incidence of HBV infection in adults is expected to decline by less than 5% over the next eight years. By 2008, over 150,000 new infections will occur annually in the United States alone and even more are expected in Europe and Japan. These individuals will constitute a tremendous reservoir of virus, from which as many as 20,000 to 40,000 chronic infections will arise per year. Clearly, despite the availability of a vaccine, chronic HBV infection will continue to be a serious health problem for many years to come.
Current therapies for chronic HBV include alpha interferon (IFN-α) and lamivudine. These therapies are judged by their abilities to reduce viral load and bring about seroconversion or the loss of the HBe antigen, a marker of HBV replication and high-titre viremia. IFN-α can eliminate HBe, but only in about one third of patients, those with low viral burdens. This treatment is costly and is associated with significant unpleasant side effects. Lamivudine is a small molecule anti-viral agent that is very well tolerated when administered orally. This compound is effective in reducing viral load in patients, but relatively few patients respond with loss of HBe, and discontinuation of therapy usually leads to increase in viral load. On the other hand, continued therapy can lead to selection for lamivudine resistant mutant variants. Combination therapy with IFN-α and lamivudine has not shown enhanced efficacy. Clearly, a successful immunotherapy to treat HBV infection is highly desirable.